January 17, 2018

Health roundup: Alzheimer's edition

Alzheimer's disease is caused by immune cells in the brain triggered by inflammation, according to a breakthrough discovery. Experiments found destroying specific cells - known as microglia - reduced the formation of clumps of amyloid beta that form in Alzheimer's and destroy memory. These are the rogue proteins believed to lie at the root of the devastating neurological illness. The researchers found the microglia release specks of a protein called ASC in response to it. They stick to the amyloid beta protein - boosting its production.

Prof Heneka, of the University of Bonn, Germany, said this may even occur in the very early stages of Alzheimer's. In tests an antibody that blocked ASC from binding to amyloid beta stopped it from forming into damaging clumps. The study published in Nature found this worked in live mice as well as cells grown in the laboratory.

Speaking from Germany, Prof Heneka said: 'The hope would be to interfere with disease progression and spreading of pathology by counteracting or interfering with the NLRP3 inflammasome or ASC specks. 'I would hope - given it is possible to develop a safe and brain penetrant NLRP3 inhibitor - this could be tested in the next five to 10 years from now.'

A drug developed for type 2 diabetes has "significantly reversed memory loss" in mice with Alzheimer's disease, and researchers now want to test it on humans. The treatment is exciting for scientists because it works by protecting the brain cells attacked by Alzheimer's disease in three separate ways, rather than relying on a single approach. The drug, which is referred to only as 'triple receptor agonist', or TA, in the paper, acts in multiple ways to protect the brain from degeneration, by activating GIP-1, GIP, and glucagon receptors at the same time. And seeing as the drug has already been tested and approved for use in humans, it's something that could hit the market a lot faster than other experimental treatment options.....

Researchers identify molecular target of J147, which is nearing clinical trials to treat Alzheimer’s disease. The experimental drug J147 is something of a modern elixir of life; it's been shown to treat Alzheimer's disease and reverse aging in mice and is almost ready for clinical trials in humans. Now scientists have solved the puzzle of what, exactly, J147 does. They report that the drug binds to a protein found in mitochondria, the energy-generating powerhouses of cells. In turn, they showed, it makes aging cells, mice and flies appear more youthful.

Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer's disease. While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer's disease and could provide clues to developing novel therapeutics for the disorder....Schubert emphasized that his team's findings were conducted in exploratory laboratory models, and that the use of THC-like compounds as a therapy would need to be tested in clinical trials.

In separate but related research, his lab found an Alzheimer's drug candidate called J147 that also removes amyloid beta from nerve cells and reduces the inflammatory response in both nerve cells and the brain. It was the study of J147 that led the scientists to discover that endocannabinoids are involved in the removal of amyloid beta and the reduction of inflammation.

For the first time ever, scientists have shown that healthy mice who shared blood with Alzheimer's-suffering mice also developed the disease. It showed that dangerous beta-amyloid proteins could travel through blood. The team in Canada surgically attached the two mice - one healthy, one suffering - found that the healthy mouse who shared blood with a mouse with Alzheimer's plaques did indeed develop plaques of beta-amyloid protein in their blood. The finding emerged from their study which also showed that Alzheimer's could start in other parts of the body - like the liver or kidney - before traveling up to the brain like cancer. However, lead author Professor Weihong Song said people should not be alarmed about Alzheimer’s being ‘caught’ by people who have had blood transfusions.

Cleaning out ‘rust’ from the brain could be a way to slow and even prevent the degenerative disease Alzheimer’s, according to new research that pinpoints iron as its so-far elusive potential driver. Previous research has long linked Alzheimer’s to a build-up in amyloid protein fragments in the brain that are normally broken down in healthy brains. But efforts to treat Alzheimer’s by using drugs that reduce amyloid levels have so far failed, leading to speculation that something else is driving the disease.

New research from the Florey Institute of Neuroscience and Mental Health and the University of Melbourne has found that iron might be the culprit. Iron has a special property that allows it to exchange electrons, which is crucial in allowing our bodies to generate energy from oxygen and fuels such as sugars. But it can also damage neurons in the same way that iron metal rusts in the presence of oxygen.
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The researchers used cutting edge magnetic resonance imaging techniques to measure iron levels in the brain. They found that people with high levels of iron in combination with high levels of amyloid were suffering rapid cognitive decline, but that people with high levels of amyloid but low levels of iron in the brain, were stable. They are now going to carry out a five year trial to test whether an anti-iron drug can slow the progress of Alzheimer’s, in what would be a major breakthrough in finding a treatment.

Dr Ayton cautions that the amount of iron in a person’s brain appears unrelated to their iron intake or iron levels in the blood. People therefore shouldn’t be cutting down on iron in response to these results. It also means that levels of iron in the blood aren’t an indicator of Alzheimer’s risk.

Researchers analyzed brain samples from patients at memory clinics and found that the presence of healthy dendritic spines -- connections between neurons -- provide protection against Alzheimer's in people whose brains have proteins associated with the disease. The study's lead author, Jeremy Herskowitz, an assistant professor with the University of Alabama at Birmingham School of Medicine's department of neurology said, "One of the precursors of Alzheimer's is the development in the brain of proteins called amyloid and tau, which we refer to as the pathology of Alzheimer's. "However, about 30 percent of the aging population have amyloid and tau buildup but never develop dementia. Our study showed that these individuals had larger, more numerous dendritic spines than those with dementia, indicating that spine health plays a major role in the onset of disease.....The new findings provide "a target for drugs that would be designed to support and maintain dendritic spine health in an effort to rebuild neurons or prevent their loss."

Neurons, which are brain cells, are constantly sending out dendritic spines in search of other neurons. When they connect, a synapse -- an exchange of information -- occurs between neurons. This is the basis for memory and learning, the researchers explained. Healthy dendritic spines could be genetic, or the result of beneficial lifestyle habits -- such as good diet and exercise -- which are known to reduce the risk of dementia.

In a study of more than 7,000 people, researchers from Israel found that dementia was 51 percent more common among people with lupus and that lupus patients of ALL ages are more likely to suffer crippling memory loss. The autoimmune disease is hard to diagnose, because it comes with so many symptoms, sometimes including a 'brain fog'. Corticosteroids are used to treat lupus, but can also cause memory problems.

A two-year study study by New York University researchers of 208 people between ages 55 and 90 found that those with sleep apnea are at higher risk of developing Alzheimer's disease. The link was found in 104 people. This is due to a build up of a toxic protein in their brain called beta-amyloid which triggers Alzheimer's, the progressive brain disease known for slowly causing impairment in memory and cognitive function.

But experts say there is a silver lining: the study showed treatments used to calm the snoring and increase oxygen flow may be able to prevent Alzheimer's disease. If left untreated, the oxygen deprivation from sleep apnea can result in a growing number of health problems, including high blood pressure, stroke, heart failure, diabetes and heart attacks.

Staying active in later life could protect against dementia, as frail older people more than triple their risk of the disease. A study has found people classed as frail in middle and old age are 3.5 times more likely to be diagnosed with Alzheimer’s disease or dementia a decade later. This may come from insulin resistance, which makes people frail by speeding up the natural loss of muscle mass which happens in older age. People with muscle weakness are more likely to have high blood sugar levels, caused by their resistance to insulin, which is also a cause of dementia. Frail people also suffer from inflammation, which is a reaction of the immune system believed to lead to the brain changes seen in dementia.

The billionaire is investing $50 million of his personal money in the London-based Dementia Discovery Fund, which is a private-public collaboration that invests in innovative dementia research. He plans to invest at least another $50 million into other startups that are working on “less mainstream” approaches, but these have not yet been identified.